解析骨转换与葡萄糖稳态之间的关系：一项基于人群的前瞻性双胞胎研究。
Disentangling the relationship between bone turnover and glucose homeostasis: A prospective, population-based twin study.
作者信息
Dalgård Christine, Hansen Morten S, Möller Sören, Kyvik Kirsten O, Frost Morten
机构信息
The Danish Twin Registry, Department of Public Health, University of Southern Denmark, Denmark.
Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.
出版信息
Bone Rep. 2021 Feb 5;14:100752. doi: 10.1016/j.bonr.2021.100752. eCollection 2021 Jun.
BACKGROUND
Biochemical markers of bone turnover are lower in patients with type 2 diabetes, which may be explained by genetic variants being associated with type 2 diabetes and bone turnover as well as environmental factors. We hypothesized that bone turnover markers associate with and predict changes in glucose homeostasis after control for genetics and shared environment.
METHODS
1071 healthy, non-diabetic (at baseline, 1997-2000) adult mono- and dizygotic twins participating in the prospective study GEMINAKAR were reassessed between 2010 and 2012 with clinical evaluation, biochemical tests and oral glucose tolerance test. Fasting bone turnover markers (CTX, P1NP and osteocalcin) were measured. The association between bone turnover, glucose homeostasis and the ability of bone turnover markers to predict changes in glucose homeostasis were assessed in cross-sectional and longitudinal analyses. Analyses were performed both at an individual level and adjusted for shared environmental and genetic factors.
RESULTS
Glucose levels increased with age, and 33 (3%) participants had developed type 2 diabetes at follow-up. In women, bone turnover markers increased with age, whereas for men only osteocalcin increased with age. Bone turnover markers were not associated with fasting glucose, insulin, or HOMA-IR at baseline or follow-up before or after adjustment for age, sex, BMI, smoking, and use of medication at baseline. Variation in bone turnover markers was mainly explained by unique environmental factors, 70%, 70% and 55% for CTX, P1NP and osteocalcin, respectively, whereas additive genetic factors explained 7%, 13% and 45% of the variation in CTX, P1NP and osteocalcin.
CONCLUSIONS
Bone turnover markers were not associated with baseline plasma glucose levels and did not predict changes in glucose homeostasis. Variation in bone turnover markers is mainly explained by environmental factors, however, compared to CTX and P1NP, genetic factors have a larger impact on osteocalcin levels.
背景
2型糖尿病患者的骨转换生化标志物较低，这可能是由于与2型糖尿病和骨转换相关的基因变异以及环境因素所致。我们假设，在控制遗传因素和共同环境因素后，骨转换标志物与葡萄糖稳态的变化相关并可预测其变化。
方法
对参与前瞻性研究GEMINAKAR的1071名健康、非糖尿病（基线时，1997 - 2000年）的成年单卵和双卵双胞胎在2010年至2012年期间进行重新评估，包括临床评估、生化检测和口服葡萄糖耐量试验。测量空腹骨转换标志物（CTX、P1NP和骨钙素）。在横断面和纵向分析中评估骨转换、葡萄糖稳态之间的关联以及骨转换标志物预测葡萄糖稳态变化的能力。分析在个体水平进行，并针对共同环境和遗传因素进行了调整。
结果
血糖水平随年龄增长而升高，33名（3%）参与者在随访时患2型糖尿病。在女性中，骨转换标志物随年龄增加，而在男性中只有骨钙素随年龄增加。在调整年龄、性别、BMI、吸烟和基线用药情况前后，骨转换标志物在基线或随访时与空腹血糖、胰岛素或HOMA - IR均无关联。骨转换标志物的变异主要由独特环境因素解释，CTX、P1NP和骨钙素分别为70%、70%和55%，而加性遗传因素分别解释了CTX、P1NP和骨钙素变异的7%、13%和45%。
结论
骨转换标志物与基线血浆葡萄糖水平无关，也不能预测葡萄糖稳态的变化。骨转换标志物的变异主要由环境因素解释，然而，与CTX和P1NP相比，遗传因素对骨钙素水平的影响更大。
Zotero 插件